Preclinical PET imaging of HIP/PAP using 1'-18F-fluoroethyl-β-D-lactose
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Shaobo Yao1,2,*, Yaping Luo1,2,*, Zhenzhong Zhang1,2, Guilan Hu1,2, Zhaohui Zhu1,2 and Fang Li1,2
1Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China
2Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, 100730, China
*These authors have contributed equally to this work
Fang Li, email: [email protected]
Keywords: PET, 18F-FEL, HIP/PAP, automated synthesis
Received: May 17, 2016 Accepted: July 06, 2017 Published: September 06, 2017
Purpose: This study aims at preclinical evaluation of a recently reported lactose analogue, 1'-18F-fluoroethyl-β-D-lactose (18F-FEL), in binding to hepatocarcinoma-intestine-pancreas and pancreatitis-associated protein (HIP/PAP) in vitro and in vivo.
Methods: In this study, a multifunctional module was employed for the automated synthesis of 18F-FEL. Additional radiochemical purity, biodistribution, in vitro and in vivo competition, metabolic stability and micro-PET studies were performed using T3M4 and SK-BR-3 xenografts. Expression of HIP/PAP in T3M4 and SK-BR-3 tumor sections and cell lines were tested with immunohistochemistry (IHC) and western blot analysis.
Results: The synthesis of 18F-FEL was completed in 30 min, with a radiochemical yield of 20 ± 5% and specific activity of 14.2 ± 7.1 GBq/μmol. 18F-FEL exhibited high HIP/PAP-binding affinity with a half maximal inhibitory concentration (IC50) of 22.0 ± 4.0 nM. 18F-FEL demonstrated high stability and specific tumor accumulation, which was reduced by approximately 80% in a PET competition assay by co-injection of β-D-lactose. High expression of HIP/PAP was detected in T3M4 tumors and cell line, but negative result was found for SK-BR-3 cell line.
Conclusion: 18F-FEL has a high binding property to HIP/PAP, high stability and excellent pharmacokinetics in vivo and therefore warrants further evaluation in a proof-of-concept study in humans.
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